WO2005074880A1 - Holistic composition and method for reducing skin pigmentation - Google Patents
Holistic composition and method for reducing skin pigmentation Download PDFInfo
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- WO2005074880A1 WO2005074880A1 PCT/US2005/000481 US2005000481W WO2005074880A1 WO 2005074880 A1 WO2005074880 A1 WO 2005074880A1 US 2005000481 W US2005000481 W US 2005000481W WO 2005074880 A1 WO2005074880 A1 WO 2005074880A1
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
- A61K8/29—Titanium; Compounds thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/37—Esters of carboxylic acids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/60—Sugars; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/63—Steroids; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
- A61K8/645—Proteins of vegetable origin; Derivatives or degradation products thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/67—Vitamins
- A61K8/676—Ascorbic acid, i.e. vitamin C
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
- A61K8/9783—Angiosperms [Magnoliophyta]
- A61K8/9789—Magnoliopsida [dicotyledons]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
- A61K8/9783—Angiosperms [Magnoliophyta]
- A61K8/9794—Liliopsida [monocotyledons]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/70—Biological properties of the composition as a whole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/74—Biological properties of particular ingredients
- A61K2800/78—Enzyme modulators, e.g. Enzyme agonists
- A61K2800/782—Enzyme inhibitors; Enzyme antagonists
Definitions
- the present invention relates to a holistic composition and method for reducing skin pigmentation that includes multiple pigmentation inhibitors, cell protectants, and functional ingredient penetration enhancers. [0002] There is a demand for products that reduce skin pigmentation.
- Melanocytes produce melanin, or skin pigment, in two forms, the darker eumelanin, and the lighter phaeomelanin. The amount of each type of melanin determines the color and degree of pigmentation in a person's skin. [0004] Melanocytes produce melanin through a series of complex cellular processes involving the conversion of tyrosine to Dopa, shown in Figure 1. Tyrosinase is the enzyme responsible for this conversion and is the primary enzyme involved in melanin biosynthesis. Dopa is then converted to eumelanin or phaeomelanin by various biochemical pathways.
- melanin Once melanin is produced, it is transferred from melanocytes, which reside in lower layers of the epidermis, to keratinocytes which are found in the upper layers of the epidermis. This transfer occurs via melanin carrying vesicles called melanosomes.
- Tyrosinase production and activity determines the amount of melanin produced. The amount and type of melanin transferred to keratinocytes determines how pigmented a person's skin will appear. Therefore, if one desires to whiten the skin, it is useful to modulate tyrosinase production and activity, melanosome transfer of melanin, as well as the ratio of eumelanin to phaeomelanin.
- melanin serves as a protectant from the sun. Melanin absorbs harmful UV rays so that cell damage resulting from UV induced free radicals is minimized. Therefore, if the amount of melanin is decreased, it is useful to provide an alternate means of UV protection. [0007] Accordingly, there is a need to reduce skin pigmentation by modulating multiple steps in the melanin production and transfer pathways as well as means for protecting the skin once the pigmentation has been reduced. In addition, a means of increasing penetration of functional ingredients is also desirable.
- the holistic approach of the present invention improves the efficacy of skin whitening through the combined effect of the functional ingredients forming the composition of the present invention, whose functions address the multiple aspects of skin pigment production and transfer in addition to providing cell protection and enhanced penetration of the functional ingredients.
- the presently claimed invention is a composition for reducing pigmentation in skin.
- the composition includes the functional ingredients; a tyrosinase production inhibitor, a tyrosinase activity inhibitor, a competitive inhibitor of melanin polymerization, a component that inhibits the transfer of melanin to a keratinocyte, a component to alter the ratio of eumelanin to phaeomelanin, and a component to lighten the skin through exfoliation.
- the composition may contain a cell protectant that includes the functional ingredients; a matrix metalloproteinase inhibitor, an antioxidant, a sun protectant, a cell metabolism stimulant, and an inflammation inhibitor.
- the composition may also include at least one functional ingredient penetration enhancer.
- the functional ingredient penetration enhancer may be a water soluble and/or an oil soluble ingredient.
- the presently claimed invention relates to a method for reducing pigmentation in skin.
- the method includes applying a composition to the skin.
- the composition includes the functional ingredients; a tyrosinase production inhibitor, a tyrosinase activity inhibitor, a competitive inhibitor of melanin polymerization, a component that inhibits the transfer of melanin to a keratinocyte, a component to alter the ratio of eumelanin to phaeomelanin, and a component to lighten the skin through exfoliation.
- the composition may contain a cell protectant that includes the functional ingredients; a matrix metalloproteinase inhibitor, an antioxidant, a sun protectant, a cell metabolism stimulant, and an inflammation inhibitor.
- the composition may also include at least one functional ingredient penetration enhancer.
- the functional ingredient penetration enhancer may be a water soluble and/or an oil soluble ingredient.
- Figure 1 is an illustration of the melanin production pathway.
- Figure 2 shows the decreased melanin content in skin samples after treatment with the holistic composition of the presently claimed invention.
- Figure 3 shows skin models after one week of incubation with a holistic composition of the presently claimed invention.
- Figure 4 shows skin models after two weeks of incubation with a holistic composition of the presently claimed invention.
- Figure 5 is a table of results from an in vivo study demonstrating improvements in mottled pigmentation, skin tone and skin clarity.
- the present invention provides a holistic composition and a method for reducing skin pigmentation.
- This holistic approach involves inhibiting melanin production and transfer at numerous points along the biosynthetic pathway. As decreasing pigmentation in the skin leaves the skin vulnerable to
- the holistic approach also provides skin protectants.
- enhancing the penetration of these functional ingredients is also contemplated by this holistic approach.
- the invention comprises 3 broad aspects: (I) pigmentation mechanism inhibitors; (II) cell protectants; and (III) functional ingredient penetration enhancers.
- the pigmentation mechanism inhibitors of the present invention include: (1) inhibition of tyrosinase production, (2) tyrosinase activity inhibitors, (3) melanin polymerization inhibitors, (4) modifiers of the ratio of eumelanin to phaeomelanin, (5) transfer of melanosomes from melanocytes to keratinocytes inhibitors, and (6) skin exfoliators.
- Tyrosinase production inhibitors include, but are not limited to hexapeptide-2.
- tyrosinase activity inhibitors suitable for the present invention: ascorbic acid and its derivatives, such as alkyl esters of L-ascorbic acid such as L-ascorbyl palmitrate, L-ascorbyl isopalmitate, L-ascorbyl dipalmitate, L- ascorbyl isostearate, L-ascorbyl distearate, L-ascorbyl diisostearate, L-ascorbyl myristate, L-ascorbyl isomyristate, L-ascorbyl 2-ethylhexanoate, L-ascorbyl di-2- ethylhexanoate, L-ascorbyl oleate and L-ascorbyl dioleate; phosphates of
- Another way to reduce the appearance of skin pigmentation is to alter the ratio of eumelanin to phaeomelanin such that the lighter phaeomelanin predominates.
- an ingredient capable of altering the eumelanin to phaeomelanin ratio is triticum vulgare (wheat) germ extract.
- Inhibiting melanosomes from transferring melanin from the melanocytes to keratinocytes is another means of reducing the appearance of skin pigmentation. Skin pigmentation is controlled by the amount of melanosomes transferred to the keratinocytes, therefore by inhibiting this transfer, skin pigmentation will appear to be decreased.
- Botanical extracts containing lectin, including triticum vulgare (wheat) germ extracts are useful for inhibiting melanin transfer to keratinocytes.
- the cell protectants of the present invention include: (1 ) matrix metalloproteinase (MMP) inhibitors, (2) anti-oxidants, (3) sun protectants; (4) cell metabolism stimulators; and (5) inflammation and/or post-inflammatory hyperpigmentation inhibitors.
- MMP matrix metalloproteinase
- MMP inhibitors are useful as cell protectants. UV rays activate
- MMPs in the skin Overactive MMPs degrade collagen and elastin and therefore accelerate the process of skin aging. When MMP activity is inhibited, the skin is protected. Solanum tuberosum (potato) extract is one example of an ingredient that is useful for inhibiting MMP activity.
- Anti-oxidants are powerful cell protectants. Harmful free radicals are generated by UV rays as well as by normal metabolic processes. Anti-oxidants help to neutralize free radicals and thus protect cell integrity and function.
- the following ingredients, either alone or in combination, may be used as anti-oxidants: ascorbic acid and derivatives such as sodium and/or magnesium ascorbyl phosphate; helianthus annus (sunflower) seed extract; citrus unshiu peel extract; citrus medica limonum (lemon) extract; cucumis sativus (cucumber) fruit extract; glycyrrhiza glabra (licorice) extract; tocopherol, and derivatives of tocopherol such as, Sodium Vitamin E Phosphate (VEP), Lauryl Imino Dipropionic Acid Tocopheryl Phosphate, Tocopheryl Glucoside, Tocopheryl Succinate, Tocophersolan (Tocopheryl Polyethylene Glycol 1000 Succinate), Disodium Lauri
- Glycoproteins are useful ingredients for stimulating cell metabolism.
- Inhibitors of inflammation and/or post-inflammatory hyperpigmentation are also useful as cell protectants.
- the following ingredients, either alone or in combination, may be used to inhibit inflammation and associated hyperpigmentation: alpha glucan oligosaccharide; dipotassium glycyrrhizinate; glycyrrhiza glabra (licorice) extract; allantoin; avena sativa (oat) kernel extract; morus alba (mulberry) extract; and cucumis sativus (cucumber) fruit extract.
- the holistic approach to reducing skin pigmentation of the present invention also addresses the aspect of delivery of the above functional ingredients.
- the dual penetration enhancing system includes a water soluble penetration enhancer in the water phase of the product and an oil soluble penetration enhancer in the oil phase of the product.
- An example of a suitable water soluble penetration enhancer is ethoxydiglycol.
- An example of a suitable oil soluble penetration enhancer is a PPG-12/SMDI copolymer.
- the present invention is suitable for reducing overall pigmentation as well as for ameliorating uneven pigmentation.
- the form that the present invention may take includes, but is not limited to: a cream, a lotion, a toner, a bar, a paste, or any other medium suitable for topical administration to the skin.
- the composition of the present invention may be applied to the entire body, including the face.
- the composition may be applied as needed or alternatively, as part of a skin care routine.
- the composition is applied weekly. More preferably, the composition is applied once or twice daily.
- the preferred mode is once in the morning and once in the evening.
- the compositions may be the same or different for each application. For example, the same composition may be applied twice daily or alternately, one composition may be applied in the morning and a second, different composition, may be applied in the evening.
- the method of the present invention includes applying the composition described above to the skin.
- Figure 2 illustrate the reduction in melanin content following treatment with three different formulas of holistic compositions, the active ingredients of which are shown in Tables 1 -3.
- the graph in Figure 2 illustrates the effectiveness of the present invention in reducing melanin content in skin. All three formulas tested reduced melanin content by over 30% compared to control.
- Table 4 shows another exemplary formula.
- the active ingredients of formulas 1-4 are given in percentage of the total volume. However, one skilled in the art may alter the percentages to suit the particular type of composition desired. Further, the vehicles, buffers, fragrance, etc., that may be used with the present invention are well known and easily determined by one skilled in the art. Table 1
- FIG. 3 and 4 a 3-D skin model is shown after incubation with a holistic composition of formula 2 for one and two weeks, respectively, compared to control.
- the black spots in the skin models are melanosome-laden keratinocytes at the surface of the model skin.
- the model shown is representative of the results obtained in the efficacy testing.
- the change in the appearance of pigmentation of the treated skin was greater than the percentage change in melanin content. The reason for this is two-fold.
- melanosome transfer inhibition and (2) an alteration of the ratio of eumelanin to phaeomelanin, leading to a predominance of the lighter phaeomelanin, are responsible for the dramatic decrease in the appearance of pigmentation.
- melanosome transfer inhibition theory although melanin is still being produced, it is not transferred to the keratinocytes. Therefore, although the melanin is present, it is not visible and the skin appears to be less pigmented than it actually is.
- an alteration in the ratio of eumelanin to phaeomelanin causes the skin to appear lighter.
- Example 2 An in vivo study was conducted in which changes in skin clarity, skin tone and mottled pigmentation were measured. Fifty-six female subjects, were studied for a period of twelve weeks. The subjects were between 25 and 65 years of age and were examined for the presence of mild to moderate mottled hyper-pigmentation on the face.
- a 10 cm analog scale was used where a score of zero indicated no mottled hyper-pigmentation and a score of ten indicated very dark, extensive pigmentation.
- Subjects with a score between 3 and 8 qualified to participate in the study and these initial scores were used as baseline values for the study.
- the subjects were treated with a skin whitening regimen containing four whitening products which were applied twice daily, three products in the morning and three in the evening, for 12 weeks. Changes in mottled pigmentation, skin clarity and skin tone were measured by a clinical grader at 2, 4, 8 and 12 weeks. The results of the study were reported as a percentage change from baseline and are shown in Figure 5. A significant improvement in skin tone, skin clarity and mottled pigmentation was recorded as early as 2 weeks into the study.
- the present invention provides a holistic approach to reducing skin pigmentation by targeting multiple pathways of melanin production and transfer.
- cell protectants and enhanced penetration of functional ingredients are also provided.
Abstract
Description
Claims
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN2005800034346A CN1913866B (en) | 2004-01-30 | 2005-01-07 | Holistic composition and method for reducing skin pigmentation |
JP2006551115A JP2007519722A (en) | 2004-01-30 | 2005-01-07 | Overall composition and method for reducing skin pigmentation |
US11/502,871 US20070087448A1 (en) | 2004-02-16 | 2006-08-11 | Biological profiles and methods of use |
HK07106004.4A HK1100896A1 (en) | 2004-01-30 | 2007-06-06 | Holistic composition and method for reducing skin pigmentation |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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US10/769,556 US7429391B2 (en) | 2004-01-30 | 2004-01-30 | Holistic composition and method for reducing skin pigmentation |
US10/769,556 | 2004-01-30 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US11/502,871 Continuation-In-Part US20070087448A1 (en) | 2004-02-16 | 2006-08-11 | Biological profiles and methods of use |
Publications (2)
Publication Number | Publication Date |
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WO2005074880A1 true WO2005074880A1 (en) | 2005-08-18 |
WO2005074880B1 WO2005074880B1 (en) | 2005-12-08 |
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Application Number | Title | Priority Date | Filing Date |
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PCT/US2005/000481 WO2005074880A1 (en) | 2004-01-30 | 2005-01-07 | Holistic composition and method for reducing skin pigmentation |
Country Status (7)
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US (1) | US7429391B2 (en) |
JP (1) | JP2007519722A (en) |
KR (1) | KR20060130631A (en) |
CN (1) | CN1913866B (en) |
HK (1) | HK1100896A1 (en) |
TW (1) | TWI361084B (en) |
WO (1) | WO2005074880A1 (en) |
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JP2008237045A (en) * | 2007-03-26 | 2008-10-09 | Shiseido Co Ltd | Three-dimensional cultured pigmentation skin model, method for producing the same and method for evaluating localization, excretion, metabolism and degradation of melanin using three-dimenensional cultured pigmentation skin model |
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CN104055685B (en) * | 2014-06-22 | 2015-07-15 | 广州悠美生物科技有限责任公司 | Bioactive micro-molecule polypeptide keratin essence |
Also Published As
Publication number | Publication date |
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KR20060130631A (en) | 2006-12-19 |
JP2007519722A (en) | 2007-07-19 |
HK1100896A1 (en) | 2007-10-05 |
US20050169860A1 (en) | 2005-08-04 |
CN1913866A (en) | 2007-02-14 |
TW200526263A (en) | 2005-08-16 |
CN1913866B (en) | 2013-03-13 |
US7429391B2 (en) | 2008-09-30 |
TWI361084B (en) | 2012-04-01 |
WO2005074880B1 (en) | 2005-12-08 |
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